Acetic Acid → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)(1-methylazetidin-3-yl)methanol

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Reaction Steps

To a flask containing azetidin-3-yl(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol (252 mg, 0.49 mmol, Example 124) was added MeOH (5 mL), formaldehyde (0.5 mL, 6.72 mmol), acetic acid (0.15 mL, 2.62 mmol) and sodium cyanoborohydride (1 M solution in THF, 1 mL, 1 mmol) at room temperature. The reaction mixture was stirred at room temperature for 24 hours and then the contents were concentrated to dryness and the residue was dissolved in DCM. 1 N Aqueous NaOH was then added to adjust the pH of the solution to pH 10. The aqueous portion was extracted with DCM (3×25 mL) and CHCl3 (2×25 mL). The organics were combined, washed with brine, dried over MgSO4, filtered and concentrated to dryness. The residue was purified by FCC (2% 2 M NH3-MeOH increasing to 10% 2 M NH3-MeOH) to provide the title compound as an off white solid. 1H NMR (500 MHz, CDCl3) δ 8.34 (d, J=2.0 Hz, 1H), 7.75 (d, J=8.7 Hz, 1H), 7.48-7.52 7.50 (m, 3H), 7.44-7.32 (m, 3H), 4.35 (s, 2H), 4.06 (s, 3H), 3.75 (s, 3H), 3.56-3.47 (m, 1H), 3.46-3.36 (m, 1H), 3.31-3.17 (m, 1H), 3.12-3.01 (m, 1H), 3.00-2.90 (m, 1H), 2.31 (s, 3H); MS (ESI): mass calcd: Chemical Formula: C26H25ClF3N5O2, Exact Mass: 531.2. m/z found 532.1 [M+H]+.

Provenance & Evidence